The Ketogenic Diet

Peterman, M. G.

doi:10.1001/jama.1928.02690450007003

Cited by 29 publications

(13 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Epilepsy Management With the Ketogenic Dietmentioning

confidence: 99%

“…It is interesting that the anticonvulsant effects of the KD can dissipate rapidly in patients who experience a rise in blood glucose levels, i.e. those who gain weight on the diet or who consume carbohydrates (Peterman 1928;Lennox 1960;Freeman et al 2000). We suggest that the seizure protective effects of the KD are largely dependent on the maintenance of reduced blood glucose levels that are also associated with reduced body weight (Livingston 1972;Greene et al 2001).…”

Section: Epilepsy Management With the Ketogenic Dietmentioning

confidence: 99%

“…Since prolonged fasting is of limited therapeutic value in epilepsy management, the high fat, low carbohydrate ketogenic diet (KD) was developed to mimic the physiological effects of fasting without starvation (Wilder 1921; Peterman 1925, 1928; Lennox 1960). The KD is remarkably effective in managing intractable seizures in children and may also be effective therapy for seizure disorders in adults (Nordli and De Vivo 1997; Vining 1997; Sirven et al .…”

Section: Epilepsy Management With the Ketogenic Dietmentioning

confidence: 99%

See 2 more Smart Citations

Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies

Greene

Todorova

Seyfried

2003

Journal of Neurochemistry

156

131

View full text Add to dashboard Cite

Brain cells are metabolically flexible because they can derive energy from both glucose and ketone bodies (acetoacetate and b-hydroxybutyrate). Metabolic control theory applies principles of bioenergetics and genome flexibility to the management of complex phenotypic traits. Epilepsy is a complex brain disorder involving excessive, synchronous, abnormal electrical firing patterns of neurons. We propose that many epilepsies with varied etiologies may ultimately involve disruptions of brain energy homeostasis and are potentially manageable through principles of metabolic control theory. This control involves moderate shifts in the availability of brain energy metabolites (glucose and ketone bodies) that alter energy metabolism through glycolysis and the tricarboxylic acid cycle, respectively. These shifts produce adjustments in gene-linked metabolic networks that manage or control the seizure disorder despite the continued presence of the inherited or acquired factors responsible for the epilepsy. This hypothesis is supported by information on the management of seizures with diets including fasting, the ketogenic diet and caloric restriction. A better understanding of the compensatory genetic and neurochemical networks of brain energy metabolism may produce novel antiepileptic therapies that are more effective and biologically friendly than those currently available.

show abstract

Section: Epilepsy Management With the Ketogenic Dietmentioning

confidence: 99%

Section: Epilepsy Management With the Ketogenic Dietmentioning

confidence: 99%

Section: Epilepsy Management With the Ketogenic Dietmentioning

confidence: 99%

See 1 more Smart Citation

Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies

Greene

Todorova

Seyfried

2003

Journal of Neurochemistry

156

131

View full text Add to dashboard Cite

show abstract

“…Since fasting produces ketonemia, it was originally thought that ketone bodies (β-hydroxybutyrate and acetoacetate) might underlie the antiepileptic effects of fasting [27,30]. Consequently, high fat, low protein, low carbohydrate KDs were developed to mimic the physiological effects of fasting [25,27,31,32]. Although the KD significantly elevates circulating ketone body levels, later studies showed that ketone bodies alone were unable to account for the antiepileptic and anticonvulsant effects of the KD in humans or in animal epilepsy models [20,31,33-38].…”

Section: Introductionmentioning

confidence: 99%

Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies

et al. 2004

View full text Add to dashboard Cite

BackgroundThe high fat, low carbohydrate ketogenic diet (KD) was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR) inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted (SD-UR) or restricted (SD-R), and either a KD unrestricted (KD-UR) or restricted (KD-R). All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once/week over a nine-week treatment period.ResultsBody weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p < 0.001) reduced in the SD-R and KD-R groups. Plasma β-hydroxybutyrate levels were significantly (p < 0.001) increased in the SD-R and KD-R groups compared to their respective UR groups. Seizure susceptibility remained high in both UR-fed groups throughout the study, but was significantly reduced after three weeks in both R-fed groups.ConclusionsThe results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone bodies for energy is predicted to manage EL epileptic seizures through multiple integrated changes of inhibitory and excitatory neural systems.

show abstract

“…Wilder (2) suggested that fasting‐associated seizure protection may arise from the long‐term persistence of ketonemia. Further studies showed that a high‐fat, low‐protein, low‐carbohydrate ketogenic diet (KD) could produce ketonemia and protect children against seizures (1,3,4). Although several studies have since confirmed the antiseizure efficacy of the KD, it remains unclear how fasting or the KD control seizures or how they affect the epileptogenic process (5–9).…”

mentioning

confidence: 99%

Caloric Restriction Inhibits Seizure Susceptibility in Epileptic EL Mice by Reducing Blood Glucose

et al. 2001

View full text Add to dashboard Cite

Summary:Purpose: Caloric restriction (CR) involves underfeeding and has long been recognized as a dietary therapy that improves health and increases longevity. In contrast to severe fasting or starvation, CR reduces total food intake without causing nutritional deficiencies. Although fasting has been recognized as an effective antiseizure therapy since the time of the ancient Greeks, the mechanism by which fasting inhibits seizures remains obscure. The influence of CR on seizure susceptibility was investigated at both juvenile (30 days) and adult (70 days) ages in the EL mouse, a genetic model of multifactorial idiopathic epilepsy.Methods: The juvenile EL mice were separated into two groups and fed standard lab chow either ad libitum (control, n ‫ס‬ 18) or with a 15% CR diet (treated, n ‫ס‬ 17). The adult EL mice were separated into three groups; control (n ‫ס‬ 15), 15% CR (n ‫ס‬ 6), and 30% CR (n ‫ס‬ 3). Body weights, seizure susceptibility, and the levels of blood glucose and ketones (␤-hydroxybutyrate) were measured over a 10-week treatment period. Simple linear regression and multiple logistic regression were used to analyze the relations among seizures, glucose, and ketones.Results: CR delayed the onset and reduced the incidence of seizures at both juvenile and adult ages and was devoid of adverse side effects. Furthermore, mild CR (15%) had a greater antiepileptogenic effect than the well-established high-fat ketogenic diet in the juvenile mice. The CR-induced changes in blood glucose levels were predictive of both blood ketone levels and seizure susceptibility.Conclusions: We propose that CR may reduce seizure susceptibility in EL mice by reducing brain glycolytic energy. Our preclinical findings suggest that CR may be an effective antiseizure dietary therapy for human seizure disorders.

show abstract

The Ketogenic Diet

Cited by 29 publications

References 13 publications

Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies

Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies

Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies

Caloric Restriction Inhibits Seizure Susceptibility in Epileptic EL Mice by Reducing Blood Glucose

Contact Info

Product

Resources

About